The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity

  1. Leiqiong Gao
  2. Jing Zhou
  3. Sen Yang
  4. Lisha Wang
  5. Xiangyu Chen
  6. Yang Yang
  7. Ren Li
  8. Zhiwei Pan
  9. Jing Zhao
  10. Zhirong Li
  11. Qizhao Huang
  12. Jianfang Tang
  13. Li Hu
  14. Pinghuang Liu
  15. Guozhong Zhang
  16. Yaokai Chen
  17. Lilin Ye

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Abstract

The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n  = 10, moderate, n  = 32, severe, n  = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (T FH ) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific T H 1 and CD8 + T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated T FH responses; however, the virus-specific T H 1 and CD8 + T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.

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  1. Version published to 10.1038/s41392-021-00525-3
  2. ScreenIT

    SciScore for 10.1101/2020.09.05.20187435: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: The 59 COVID-19 convalescent donors enrolled in the study were provided written informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Then these ELISA plates were incubated with anti-human IgG HRP antibody (Bioss Biotech, 0297D) at room temperature for 1 hour.
    anti-human IgG
    suggested: None
    CXCL13 ELISA: The costar 96-well clear plates (Costar, 42592) were coated with 2μg/mL CXCL13 monoclonal antibody (Sino Biological, 70057-MM13) overnight at 4°C.
    CXCL13
    suggested: None
    Anti-rabbit IgG antibody was used at a 1:3000 dilution.
    Anti-rabbit IgG
    suggested: None
    Antibodies used in the T cell and B cells surface marker staining are listed in Table S5 and S6.
    S6
    suggested: None
    Software and Algorithms
    SentencesResources
    Peripheral blood mononuclear cells (PBMCs) were isolated by density-gradient sedimentation using Ficoll-Paque(Haoyang Biological, Tianjin, China).
    Ficoll-Paque(Haoyang Biological
    suggested: None
    Then washed three times with FACs and acquired by FACS Verse (BD Biosciences, San Jose, CA).
    FACs
    suggested: (FACS, RRID:SCR_000055)
    Data were analyzed by FlowJo software (Version 10.0.8, Tree Star Inc., Ashland).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Quantification and Statistical analysis: FlowJo 10 and GraphPad Prism 8.0.2 are used for data and statistical analyses.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.09.05.20187435v1 on medRxiv